Discover and read the best of Twitter Threads about #diseasetolerance
Most recents (3)
Peer-reviewed paper out today! Our research created induced pluripotent stem cells from bats, revealing an unusual entanglement between bats & viruses. Provides new insights into bat biology & virus-host relationships. #batstemcells #viralbiology @CellCellPress @IcahnMountSinai
Bats have fascinated humans for centuries, but how they tolerate viruses remains a mystery. We investigate evolutionary adaptations of bats to deal with viral infections. #batimmunesystem #viralpathogens Photo: Daniel Whitby 2/ 
As the elderly are more susceptible to #COVID19 w/ signs of lung #inflammation, here's a thread about our @virusesimmunity 2016 flu paper on #antiviral resistance, excessive lung #inflammation, & a strategy to boost disease tolerance! science.sciencemag.org/content/352/62…
First we demonstrated that monos & macs from older adults have impaired type I IFN (antiviral) & #ISG responses but intact cytokine responses after #flu infection. To probe the possible in vivo consequences of weak #IFN responses in the face of robust inflammation...
... we made a mouse model that mimicked this immune response in the elderly (Mx1+/+ mice w/ genetic deletion of tlr7, mavs). Failure to induce type I IFN led to high viral titer, 2º bacterial infection, severe lung inflammation, and death.
Investigation of transcriptional differences between healthy infected vs morbid infected vs uninfected identified many non-immune pathways unregulated in healthy infected (matching, again, disease tolerance mechanisms rather than antagonistic inflammatory responses)
One major upregulated pathway was iron metabolism - and iron supplementation of diet was sufficient to be completely protective up to 1000x LD100 (>10^10 cfu) of Citrobacter, even with comparable pathogen burden in stool
Dietary iron protected from intestinal epithelial damage, prevented systemic dissemination of Citrobacter, and lowered expression of virulence genes in Citrobacter through an indirect mechanism (not acting on Citrobacter directly) and independently of microbiota
